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Article
Nature Biotechnology - 24, 1573 - 1580 (2006)
Published online: 19 November 2006; | doi:10.1038/nbt1256

The genome and transcriptomes of the anti-tumor agent Clostridium novyi-NT

Chetan Bettegowda1, 3, 4, Xin Huang1, 4, Jimmy Lin1, 4, Ian Cheong1, Manu Kohli1, Stephen A Szabo1, Xiaosong Zhang1, Luis A Diaz Jr1, Victor E Velculescu1, Giovanni Parmigiani2, Kenneth W Kinzler1, Bert Vogelstein1 & Shibin Zhou1

1  The Howard Hughes Medical Institute, The Ludwig Center for Cancer Genetics & Therapeutics at The Sidney Kimmel Comprehensive Cancer Center, and Department of Pharmacology and Molecular Sciences, Johns Hopkins Medical Institutions, 1650 Orleans Street, Baltimore, Maryland 21231, USA.

2  Departments of Oncology, Biostatistics and Pathology, Johns Hopkins Medical Institutions, 550 North Broadway, Baltimore, Maryland 21205, USA.

3  Present address: Department of Neurology and Neurosurgery, Johns Hopkins Medical Institutions, 600 N. Wolfe Street, Baltimore, Maryland 21287, USA.

4  These authors contributed equally to this work.

Correspondence should be addressed to Shibin Zhou sbzhou@jhmi.edu

Bacteriolytic anti-cancer therapies employ attenuated bacterial strains that selectively proliferate within tumors. Clostridium novyi-NT spores represent one of the most promising of these agents, as they generate potent anti-tumor effects in experimental animals. We have determined the 2.55-Mb genomic sequence of C. novyi-NT, identifying a new type of transposition and 139 genes that do not have homologs in other bacteria. The genomic sequence was used to facilitate the detection of transcripts expressed at various stages of the life cycle of this bacterium in vitro as well as in infections of tumors in vivo. Through this analysis, we found that C. novyi-NT spores contained mRNA and that the spore transcripts were distinct from those in vegetative forms of the bacterium.

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Nature Biotechnology
ISSN: 1087-0156
EISSN: 1546-1696
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